DESCRIPTION (From the principal investigator's abstract): The long-term objective of the proposed research is to elucidate the mechanisms by which neuronal activity shapes synaptic connections during development of the visual system. The central hypothesis is that activation of N-methyl-d-aspartate (NMDA) receptors on cells of the LGN by synchronously active retinal afferents allows the entry of Ca++ into the postsynaptic cell, stimulating the production of NO by nitric oxide synthase (NOS). NO diffuses to the presynaptic terminal and acts as a retrograde messenger to potentiate synaptic transmission and stabilize synapses. The proposed experiments address the role of NO as a putative retrograde messenger during activity-dependent refinement of the projections from the retina to the LGN in ferrets. The specific aims of this project are to examine: 1. the role of NO in shaping presynaptic retinal axon arbors; 2. the role of NO in mediating synaptic transmission and potentiation/depression in the developing LGN; 3. the role of NO in shaping postsynaptic LGN cell morphology; 4. The role of NO in dynamic remodeling of retinal axon arbors and LGN cell dendrites.